Lipid peroxidation regulates long-range wound detection through 5-lipoxygenase in zebrafish

Nat Cell Biol. 2020 Sep;22(9):1049-1055. doi: 10.1038/s41556-020-0564-2. Epub 2020 Aug 31.


Rapid wound detection by distant leukocytes is essential for antimicrobial defence and post-infection survival1. The reactive oxygen species hydrogen peroxide and the polyunsaturated fatty acid arachidonic acid are among the earliest known mediators of this process2-4. It is unknown whether or how these highly conserved cues collaborate to achieve wound detection over distances of several hundreds of micrometres within a few minutes. To investigate this, we locally applied arachidonic acid and skin-permeable peroxide by micropipette perfusion to unwounded zebrafish tail fins. As in wounds, arachidonic acid rapidly attracted leukocytes through dual oxidase (Duox) and 5-lipoxygenase (Alox5a). Peroxide promoted chemotaxis to arachidonic acid without being chemotactic on its own. Intravital biosensor imaging showed that wound peroxide and arachidonic acid converged on half-millimetre-long lipid peroxidation gradients that promoted leukocyte attraction. Our data suggest that lipid peroxidation functions as a spatial redox relay that enables long-range detection of early wound cues by immune cells, outlining a beneficial role for this otherwise toxic process.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Arachidonic Acid / metabolism
  • Leukocytes / metabolism
  • Lipid Peroxidation / physiology*
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism
  • Wounds and Injuries / metabolism*
  • Zebrafish / metabolism*


  • Reactive Oxygen Species
  • Arachidonic Acid
  • Arachidonate 5-Lipoxygenase